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Aktuelle Dermatologie 2007; 33(8/09): 310-316
DOI: 10.1055/s-2007-966548
Originalarbeit

© Georg Thieme Verlag KG Stuttgart · New York

Anti-TNF-α-Therapie der Psoriasis mit Infliximab oder Etanercept. Klinischer, histologischer und immunhistochemischer Verlauf[1]

Anti-TNF-α-Therapy of Psoriasis with Infliximab or Etanercept. Clinical, Histological and Immunohistochemical CourseM.  Angsten1 , R.  E.  Schopf1
  • 1Universitäts-Hautklinik, Johannes Gutenberg-Universität Mainz
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Publication History

Publication Date:
23 July 2007 (online)

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Zusammenfassung

TNF-α spielt eine zentrale Rolle in der Pathogenese der Psoriasis. In vorangehenden Studien verbesserten sich psoriatische Hautläsionen unter anti-TNF-α-Therapie mit Etanercept oder Infliximab. Beide Medikamente wirken über einen unterschiedlichen, noch nicht vollständig geklärten Mechanismus und differieren bezüglich des Wirkspektrums. Diese Arbeit untersucht und vergleicht bei 12 Patienten die Effekte der Kurzzeittherapien mit Etanercept (6 Patienten) oder Infliximab (6 Patienten) auf die verschiedenen pathohistologischen bzw. klinischen Befunde der Psoriasis. Zur klinischen Betrachtung dienen PASI und Juckreiz. Hautbiopsien und deren HE- bzw. immunhistochemische Färbungen ermöglichen die Beurteilung der histologischen Befunde (Epidermisdicke, Entzündungsreaktion, Proliferations- und Differenzierungsstörung der Keratinozyten). Die deskriptive Analyse erfolgt mittels Median und Quartilen (1. und 3. Quartil). Etanercept bewirkt eine Reduktion des PASI um 8,2 (14,7; 6,7; p = 0,031). Der Juckreiz nach Behandlung mit Etanercept ist vermindert oder unverändert, die Epidermisdicke hat sich normalisiert (p = 0,031). Der gleiche Trend zeichnet sich hinsichtlich der Proliferations- und Differenzierungsstörung ab. Die epidermalen und dermalen Entzündungsparameter haben sich insgesamt betrachtet jedoch nicht verringert. Infliximab bewirkt einen Abfall des PASI um 18,5 (23,6; 12,9; p = 0,031). Auch Juckreiz und Epidermisdicke haben sich nach Therapie verbessert (jeweils p = 0,031). Die Proliferations- und Differenzierungsstörung der Keratinozyten normalisiert sich ebenfalls (für Ki-67 und Involucrin, jeweils p = 0,031). Im Gegensatz zur Etanerceptgruppe spricht in der Infliximabgruppe auch das entzündliche Infiltrat für eine Abheilung der psoriatischen Plaques (bei CD45RO+-T-Zellen, p = 0,031). Die Infliximabgruppe zeichnet sich bei allen klinischen und histologischen Befunden durch eine stärkere Verbesserung des Hautstatus aus. Seitens der Entzündungsreaktion zeigt sich hinsichtlich der CD3+-T-Zellen ein Rückgang (p = 0,032). Die dargelegten Befunde sind mit den unterschiedlichen Wirkmechanismen von Infliximab und Etanercept vereinbar und spiegeln die Schlüsselposition von TNF-α bezüglich der Psoriasis wider.

Abstract

TNF-α plays a central role in the pathogenesis of psoriasis. Recently, it has been demonstrated that psoriatic skin lesions showed improvement during anti-TNF-α-therapy with etanercept or infliximab. These agents act in a different, not yet completely understood manner. The purpose of this study was to assess the effects of short-term therapy by treating 6 patients with etanercept and another 6 patients with infliximab. In each case, the pathological, histological and clinical signs of psoriasis vulgaris were analysed and compared. PASI, pruritus, epidermal thickness, markers of cutaneous inflammation, keratinocyte proliferation and differentiation were evaluated. Treatment with etanercept: PASI was diminished by 8.2 (14.7; 6.7; p = 0.031). Pruritus after etanercept treatment remained either unchanged or was reduced. Epidermal thickness was normalized (p = 0.031). The same tendency was observed in markers of keratinocyte proliferation and differentiation, but, in general, the number of epidermal and dermal inflammatory cells did not decrease. Treatment with infliximab: PASI was diminished by 18.5 (23.6; 12.9; p = 0.031). Pruritus and epidermal thickness were diminished (p = 0.031). Markers of keratinocyte proliferation and differentiation were reduced (Ki-67 and CD45RO+ significantly, p = 0.031). In contrast to the etanercept treatment T-cells in skin were also reduced (CD45RO+-cells, p = 0.031). The patients who received infliximab showed greater improvement in all analysed clinical and histological symptoms of psoriasis. Regarding the cutaneous T-cells infiltrate, a reduction of CD3+-T-cells (p = 0.032) occurred. The results of this study correspond to the different mechanisms of action of infliximab and etanercept and outline the key position of TNF-α for psoriasis.

1 Die Arbeit bezieht sich auf Ergebnisse der gleichnamigen Dissertation von Frau Marina Angsten.

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1 Die Arbeit bezieht sich auf Ergebnisse der gleichnamigen Dissertation von Frau Marina Angsten.

Dr. Marina Angsten

Kaiser-Wilhelm-Ring 31-33

55118 Mainz

Email: marina.angsten@onlinehome.de